portal vein diameter in patients with liver cirrhosis and hepatic
TRANSCRIPT
Portal Vein Diameter in Patients with
Liver Cirrhosis and Hepatic
Encephalopathy
Elwir S, Hal H, Veith J, Schreibman I,
Kadry Z, Riley T
Abstract P246, Poster Presentation
ACG 2012 Annual Scientific Meeting and
Postgraduate Course
Las Vegas, NV
October 21, 2012
Portal Vein Diameter in Patients with Liver Cirrhosis and Hepatic Encephalopathy: Objective
• Objective: To assess the correlation between
hepatic encephalopathy (HE) with findings
detected on radiographic imaging studies and
the patient’s clinical profile
Elwir S et al. Abstract P246. Poster presentation at the 2012 ACG Annual Scientific Meeting and Postgraduate Course,
Las Vegas, NV, October 21, 2012.
Portal Vein Diameter in Patients with Liver Cirrhosis and Hepatic Encephalopathy: Methods
• Retrospective review of patients evaluated in the
liver transplant clinic in 2009 and 2010
– Excluded patients with HCC, ejection fraction <60%,
and patients who had a TIPS procedure
– Patient’s imaging studies were correlated with their
baseline demographics, medical histori, and clinical
presentation
• Variables found to be significant on univariate
analysis (P<0.05) were analyzed by multivariate
logistic regression model
Elwir S et al. Abstract P246. Poster presentation at the 2012 ACG Annual Scientific Meeting and Postgraduate Course,
Las Vegas, NV, October 21, 2012.
Portal Vein Diameter in Patients with Liver Cirrhosis and Hepatic Encephalopathy: Results
• 117 patients met inclusion criteria; divided into an
HE group (n=58) and a control group (n=59) based
on whether or not they had clinical evidence of HE
• Mean portal vein diameter:
– HE group: 12.1 2.9 mm
– Control group: 14 3.1 mm (P=0.001)
• 1-mm increase in portal vein diameter is associated
with a 15% decrease in the odds of encephalopathy
(OR 0.85; 95% CI 0.73-0.99)
Elwir S et al. Abstract P246. Poster presentation at the 2012 ACG Annual Scientific Meeting and Postgraduate Course,
Las Vegas, NV, October 21, 2012.
Portal Vein Diameter in Patients with Liver Cirrhosis and Hepatic
Encephalopathy: Results (cont)
• Significant correlation with HE on univariate analysis:
– Smaller portal vein diameter
– Smaller liver anteroposterior diameter
– Diuretic use
– Use of centrally acting medications
– Liver nodularity
• Significant correlation with HE on multivariate analysis:
– Portal vein diameter
– Use of diuretics
– Use of centrally acting medications
Elwir S et al. Abstract P246. Poster presentation at the 2012 ACG Annual Scientific Meeting and Postgraduate Course,
Las Vegas, NV, October 21, 2012.
Portal Vein Diameter in Patients with Liver Cirrhosis and Hepatic
Encephalopathy: Conclusion
• A decrease in portal vein diameter was
associated with increased risk of HE
• Identifying patients with smaller portal vein
diameter may warrant screening for HE by more
advanced psychometric testing, protein
restriction, and more aggressive control of
constipation and other factors that may
precipitate encephalopathy
Elwir S et al. Abstract P246. Poster presentation at the 2012 ACG Annual Scientific Meeting and Postgraduate Course,
Las Vegas, NV, October 21, 2012.
Probiotics in Minimal Hepatic
Encephalopathy: A Meta-Analysis
Agrawal M, Homel P, Badalov N, Mayer I,
Rahmani R
Abstract P772, Poster Presentation
ACG 2012 Annual Scientific Meeting and
Postgraduate Course
Las Vegas, NV
October 22, 2012
Probiotics in Minimal Hepatic
Encephalopathy: Objective
• Objective: Meta-analysis of studies conducted to
identify the role of probiotics in the management
of minimal hepatic encephalopathy (MHE)
Agrawal M et al. Abstract P772. Poster presentation at the 2012 ACG Annual Scientific Meeting and Postgraduate Course,
Las Vegas, NV, October 22, 2012.
Probiotics in Minimal Hepatic
Encephalopathy: Methods
• Search on Pubmed and Medview to identify
randomized controlled trials (RCT) on probiotics in
minimal hepatic encephalopathy (MHE) in last 20
years
• Eligible studies had to include at least 2 randomized
groups with a pre/post comparison of mean SD of
serum ammonia levels
– 5 studies compared probiotics vs placebo/no treatment
– 3 studies compared probiotics vs. lactulose
• Analyses done using Comprehensive Met Analysis 2.2
Agrawal M et al. Abstract P772. Poster presentation at the 2012 ACG Annual Scientific Meeting and Postgraduate Course,
Las Vegas, NV, October 22, 2012.
Probiotics in Minimal Hepatic
Encephalopathy: Results
• Treatment with probiotics was:
– Superior to placebo (P=0.006)
– Superior to lactulose (P=0.02)
• Standardized difference (95% CI):
– Probiotics vs. placebo: 0.44 (0.13, 0.75)
– Probiotics vs. lactulose: 0.32 (0.06, 0.58)
Agrawal M et al. Abstract P772. Poster presentation at the 2012 ACG Annual Scientific Meeting and Postgraduate Course,
Las Vegas, NV, October 22, 2012.
Probiotics in Minimal Hepatic
Encephalopathy: Results (cont)
Agrawal M et al. Abstract P772. Poster presentation at the 2012 ACG Annual Scientific Meeting and Postgraduate Course,
Las Vegas, NV, October 22, 2012.
Study Std diff
in
means
SE Vari-
ance
Lower
limit
Upper
limit
Z-
Value
P-
Value
Saji et al, 2011 -0.212 0.317 0.101 -0.833 0.410 -0.667 0.505
Pereg et al, 2011 0.515 0.339 0.115 -0.149 1.179 1.521 0.128
Bajaj et al, 2008 -0.121 0.444 0.197 -0.990 0.749 -0.272 0.785
Malaguamera et al,
2007
0.551 0.263 0.069 0.035 1.067 2.095 0.036
Liu et et al, 2004 8.509 1.073 1.151 6.407 10.612 7.931 0.000
0.439 0.160 0.026 0.125 0.752 2.741 0.006
Studies comparing probiotics with placebo/no treatment
Probiotics in Minimal Hepatic
Encephalopathy: Results (cont)
Agrawal M et al. Abstract P772. Poster presentation at the 2012 ACG Annual Scientific Meeting and Postgraduate Course,
Las Vegas, NV, October 22, 2012.
Standard differences and 95% CI in studies comparing
probiotics with placebo/no treatment
Saji et al, 2011 Pereg et al, 2011 Bajaj et al, 2008
Malaguamera et al, 2007 Liu et al, 2004
Standard difference in means and 95% CI
Probiotics in Minimal Hepatic
Encephalopathy: Results (cont)
Agrawal M et al. Abstract P772. Poster presentation at the 2012 ACG Annual Scientific Meeting and Postgraduate Course,
Las Vegas, NV, October 22, 2012.
Study Std diff
in
means
SE Vari-
ance
Lower
limit
Upper
limit
Z-
Value
P-
Value
Maguamera et al,
2009
0.394 0.181 0.033 0.040 0.748 2.181 0.029
Sharma et al, 2007 0.015 0.247 0.061 -0.469 0.498 0.060 0.953
Loguercio et al,
1994
0.639 0.333 0.111 -0.013 1.291 1.921 0.055
0.322 0.133 0.018 0.061 0.584 2.415 0.016
Studies comparing probiotics with lactulose
Probiotics in Minimal Hepatic
Encephalopathy: Results (cont)
Agrawal M et al. Abstract P772. Poster presentation at the 2012 ACG Annual Scientific Meeting and Postgraduate Course,
Las Vegas, NV, October 22, 2012.
Standard differences and 95% CI in studies comparing
probiotics with lactulose
Standard difference in means and 95% CI
Malaguamera et al, 2009 Sharma et al, 2007
Loguercio et al, 1994
Probiotics in Minimal Hepatic
Encephalopathy: Conclusion
• Results indicate the beneficial role of probiotics
in lowering serum ammonia levels in MHE
patients
• Results compare favorably with lactulose, with
possibly fewer adverse effects such as diarrhea
and bloating
• Large randomized controlled trials are warranted
to further validate the role of probiotics in MHE
Agrawal M et al. Abstract P772. Poster presentation at the 2012 ACG Annual Scientific Meeting and Postgraduate Course,
Las Vegas, NV, October 22, 2012.
Does Inhibitory Control Test (ICT)
Diagnose Minimal Hepatic
Encephalopathy (MHE)?
Allampati S, Prakash R, Perzynski A,
Theethira T, Mullen K
Abstract P804, Poster Presentation
ACG 2012 Annual Scientific Meeting and
Postgraduate Course
Las Vegas, NV
October 22, 2012
Inhibitory Control Test for Diagnosis of Minimal Hepatic Encephalopathy:
Objective
• Objective: To study the reliability and validity of
the Inhibitory Control Test (ITC) for the diagnosis
of minimal hepatic encephalopathy (MHE)
Allampati SK et al. Abstract P804. Poster presentation at the 2012 ACG Annual Scientific Meeting and Postgraduate
Course, Las Vegas, NV, October 22, 2012.
Inhibitory Control Test for Diagnosis of Minimal Hepatic Encephalopathy:
Methods
• 68 outpatient cirrhotics included In study
• Inclusion criterion: Presence of cirrhosis proven by biopsy
or ultrasound regardless of cause
• Exclusion criteria: Presence of overt hepatic
encephalopathy (OHE) on presentation to the clinic or
history of OHE 30 days prior
• Full batteries of the Psychometric Hepatic
Encephalopathy Score (PHES) and the Inhibitory Control
Test (ICT) were administered
• Controls for PHES were generated by testing >100
healthy volunteers Allampati SK et al. Abstract P804. Poster presentation at the 2012 ACG Annual Scientific Meeting and Postgraduate
Course, Las Vegas, NV, October 22, 2012.
Inhibitory Control Test for Diagnosis of Minimal Hepatic Encephalopathy:
Results (cont)
• Patients with cirrhosis had lower scores on all PHES
domains than the healthy control group
– Patients with cirrhosis were categorized as MHE+ if they
exhibited a score 2 SD below the healthy controls in 1
tests
– Using this criteria, 36/68 (52.9%) of the cirrhosis patients
were diagnosed as MHE+ and 32/68 (47.1%) were MHE-
• MHE+ patients performed significantly worse on ICT than
MHE- patients
• Mean ICT values for MHE+ and MHE- cirrhotics were
higher than seen in prior studies
Allampati SK et al. Abstract P804. Poster presentation at the 2012 ACG Annual Scientific Meeting and Postgraduate
Course, Las Vegas, NV, October 22, 2012.
Inhibitory Control Test for Diagnosis of Minimal Hepatic Encephalopathy:
Results (cont)
Allampati SK et al. Abstract P804. Poster presentation at the 2012 ACG Annual Scientific Meeting and Postgraduate
Course, Las Vegas, NV, October 22, 2012.
Controls
(n=104)
Cirrhotics
(n=68)
P values
Age (years) 48.9 55.6 <.001
Education (years) 14.4 12.2 <.001
NCT-A (seconds) 29.6 44.7 <.001
NCT-B (seconds) 72.3 123.3 <.001
DST (raw score) 50.4 37.3 <.001
SDT (seconds) 64.3 99.4 <.001
Comparison of PHES results between controls and cirrhotics
Inhibitory Control Test for Diagnosis of Minimal Hepatic Encephalopathy:
Results (cont)
Allampati SK et al. Abstract P804. Poster presentation at the 2012 ACG Annual Scientific Meeting and Postgraduate
Course, Las Vegas, NV, October 22, 2012.
With MHE (n=36)
Without MHE (n=32)
P values
Age (years) 57.9 53.6 .039
Education (years) 11.9 12.5 .304
NCT-A (seconds) 59.4 29.3 <.001
NCT-B (seconds) 165.5 78.9 <.001
DST (raw score) 29.3 45.8 <.001
SDT (seconds) 121.7 75.6 <.001
Response to ICT lures (number out of 40)
17.8 11.3 .006
Response to ICT targets (percentage score)
81.1% 96.1% <.001
Weighted lures 26.1 8.7 <.001
Comparison of PHES and ITC results in cirrhotics with and without MHE
Inhibitory Control Test for Diagnosis of Minimal Hepatic Encephalopathy:
Conclusions
Allampati SK et al. Abstract P804. Poster presentation at the 2012 ACG Annual Scientific Meeting and Postgraduate
Course, Las Vegas, NV, October 22, 2012.
• Prior work has supported ICT as a reliable and
valid test for the diagnosis of MHE
• Current study raises question regarding the
threshold for the diagnosis of MHE with ICT
since mean ICT values for MHE+ and MHE-
cirrhotics were higher than seen in prior studies
Effect of Computer Literacy on
Psychometric Test Performance in
the Diagnosis of Minimal Hepatic
Encephalopathy
Karanth P, Chikkanna R, Allampati S,
Prakash R, Anna K, Mullen K, Perzynski A
Abstract P807, Poster Presentation
ACG 2012 Annual Scientific Meeting and
Postgraduate Course
Las Vegas, NV
October 22, 2012
Effect of Computer Literacy on Psychometric Test Performance:
Objective
• Objective: To study the effect of computer
literacy on performance in a psychometric test
(CNS Vital Signs) used in the diagnosis of
minimal hepatic encephalopathy (MHE)
Karanth P et al. Abstract P807. Poster presentation at the 2012 ACG Annual Scientific Meeting and Postgraduate
Course, Las Vegas, NV, October 22, 2012.
Effect of Computer Literacy on Psychometric Test Performance:
Methods • Cirrhotic patients between ages of 18 - 70 years were
recruited prospectively from outpatient liver clinic
– Received thorough clinical examination and mini mental status
examination to rule out low grade overt hepatic encephalopathy
– Patients asked about educational status, computer literacy, and
handedness (left or right predominant)
– Computer literacy assessed by asking patients whether they
were frequent users, infrequent users, or non-users
• Patients subjected to paper and pencil psychometric test
battery (Psychometric Hepatic Encephalopathy Score,
PHES) and computerized psychometric test battery
called CNS Vital Signs (CNSVS; available online at
cnsvs.com) Karanth P et al. Abstract P807. Poster presentation at the 2012 ACG Annual Scientific Meeting and Postgraduate
Course, Las Vegas, NV, October 22, 2012.
Effect of Computer Literacy on Psychometric Test Performance: Results
• 57 patients recruited
– 12 (21.1%) diagnosed as MHE+ with PHES
– 11 (19.3%) diagnosed as MHE+ with CNSVS testing
• Level of education was not associated with
performance on either PHES or CNSVS tests
Karanth P et al. Abstract P807. Poster presentation at the 2012 ACG Annual Scientific Meeting and Postgraduate
Course, Las Vegas, NV, October 22, 2012.
Effect of Computer Literacy on Psychometric Test Performance: Results
(cont)
• Patient self-reported computer usage was frequent
(22.8%), infrequent (57.9%), and non-user (19.3%)
– Computer usage was not associated with education level
– Computer use had a small to moderate significant positive
association (r=0.28 to r=0.48) on nearly all domains of the
computerized and the paper and pencil tests
– Mean time to complete number connection task was lower
among frequent computer users (31.7 seconds) than
among non-computer users (60.4 seconds, P = 0.003)
– Frequent computer users were on average 18.1 seconds
faster on the computerized processing speed test (P =
0.001)
Karanth P et al. Abstract P807. Poster presentation at the 2012 ACG Annual Scientific Meeting and Postgraduate
Course, Las Vegas, NV, October 22, 2012.
Effect of Computer Literacy on Psychometric Test Performance:
Conclusion
• Higher levels of computer usage are associated with
better performance on cognitive tests in this sample
of patients with liver disease
• Magnitude of the association is similar for both
paper and pencil and computerized tests suggesting
differences in cognitive performance rather than bias
based upon testing medium
• Further research is necessary to determine how
computer use (independently of education)
influences performance in cognitive tests
Karanth P et al. Abstract P807. Poster presentation at the 2012 ACG Annual Scientific Meeting and Postgraduate
Course, Las Vegas, NV, October 22, 2012.
Outcomes in Length of Hospital Stay in
Cirrhotics Admitted for
Overt Hepatic Encephalopathy
Neff G, Kemmer N, Parkinson E,
Cece E, Christian M, Webster H,
Cooper J, Houston S, Mendoza A, Gardner J,
Alsina A, Bowers V
Abstract P926, Poster Presentation
ACG 2012 Annual Scientific Meeting and
Postgraduate Course
Las Vegas, NV
October 22, 2012
Assessing Hospital Stays in Patients with Overt Hepatic Encephalopathy:
Objective
• Objective: To retrospectively investigate
treatment regimens and their impact upon
length of hospital stay in cirrhotics admitted for
overt hepatic encephalopathy (OHE)
Neff GW et al. Abstract P926. Poster presentation at the 2012 ACG Annual Scientific Meeting and Postgraduate
Course, Las Vegas, NV, October 22, 2012.
Assessing Hospital Stays in Patients with Overt Hepatic Encephalopathy:
Methods
• Medical charts of hospitalized patients admitted with
OHE (Conn Score grade 3 or 4) from December 2010
to May 2012 were evaluated
• Patients were grouped according to medication
received prior to admission and medication received
during hospitalization
• MELD score, HE management protocol, length of stay,
time to starting a full diet, HE hospitalization number
(frequency) and days to readmission were analyzed
Neff GW et al. Abstract P926. Poster presentation at the 2012 ACG Annual Scientific Meeting and Postgraduate
Course, Las Vegas, NV, October 22, 2012.
Assessing Hospital Stays in Patients with Overt Hepatic Encephalopathy:
Results
Neff GW et al. Abstract P926. Poster presentation at the 2012 ACG Annual Scientific Meeting and Postgraduate
Course, Las Vegas, NV, October 22, 2012.
Group
(outpatient
therapyhospital
therapy)
n MELD
score
(mean)
Length
of Stay
(days)
Time to
start of
full diet
(days)
HCUP
(7,500/d)
Insured/MC
/MD costs
(8,382/d)
(1) LacLac 18 11.5 5.75 4.1 43,125 48,147
(2) RFXLac 19 12.5 3.4 2.25 25,500 28,329
(3) LacRFX 20 10.5 4.25 3.5 31,875 35,624
(4) NTLac/RFX 14 11.5 5.25 3.8 39,375 44,006
(5) NTLac 28 13 6.5 4.5 48,750 54,483
MELD, Model for End-Stage Liver Disease; HCUP, Healthcare Cost & Utilization
Project; Lac, Lactulose monotherapy; RFX, rifaximin monotherapy; Lac/RFX,
lactulose + rifaximin combination therapy; NT, no treatment
Assessing Hospital Stays in Patients with Overt Hepatic Encephalopathy:
Results (cont)
Neff GW et al. Abstract P926. Poster presentation at the 2012 ACG Annual Scientific Meeting and Postgraduate
Course, Las Vegas, NV, October 22, 2012.
• Readmission: Groups discharged with Lac
monotherpay preformed worse amongst all
groups
• Financial comparison: All Lac monotherapy
groups approached $125-150,000 US within a
six-month period
– Escalated cost was based upon frequent repeat
hospitalizations
Assessing Hospital Stays in Patients with Overt Hepatic Encephalopathy:
Conclusion
Neff GW et al. Abstract P926. Poster presentation at the 2012 ACG Annual Scientific Meeting and Postgraduate
Course, Las Vegas, NV, October 22, 2012.
• Patients maintained on RFX monotherapy
outperformed all groups and utilized less
healthcare dollars when compared to all LAC
groups
Long Term Survival Following Overt
Hepatic Encephalopathy
Neff G, Christian M, Ramirez M, Webster H,
Galambo F, Palamittam D, Parkinson E,
Cece E, Cooper J, Alsina A, Mendoza A, Kemmer N
Abstract P927, Poster Presentation
ACG 2012 Annual Scientific Meeting and
Postgraduate Course
Las Vegas, NV
October 22, 2012
Long Term Survival Following Overt
Hepatic Encephalopathy: Objective
• Objective: To compare the long-term survival
of overt hepatic encephalopathy (OHE)
patients according to post discharge HE
therapy
Neff GW et al. Abstract P927. Poster presentation at the 2012 ACG Annual Scientific Meeting and Postgraduate
Course, Las Vegas, NV, October 22, 2012.
Long Term Survival Following Overt
Hepatic Encephalopathy: Methods
• Medical charts of outpatient and hospitalized
patients admitted for OHE from December 2000 to
May 2012 were examined
• Information collected included post discharge HE
management protocol, HE hospitalization number
(frequency), and time (days) to transplant or death
Neff GW et al. Abstract P927. Poster presentation at the 2012 ACG Annual Scientific Meeting and Postgraduate
Course, Las Vegas, NV, October 22, 2012.
Long Term Survival Following Overt
Hepatic Encephalopathy: Methods
(cont)
• Four groups were identified: 1) Lactulose (Lac)
monotherapy, 2) Lac combined with rifaximin
(RFX), 3) RFX monotherapy, and, 4) No therapy
• RFX dose: Initially 1,200 mg/day dosing; later
changed to 1,100 mg/day (550 mg twice/day)
• Lac dose: 30 - 120 mL/day, adjusted to acquire 2
to 3 loose to soft bowel movements
Neff GW et al. Abstract P927. Poster presentation at the 2012 ACG Annual Scientific Meeting and Postgraduate
Course, Las Vegas, NV, October 22, 2012.
Long Term Survival Following OHE Depends on Post-Hospital Discharge
Therapy
Neff GW et al. Abstract P927. Poster presentation at the 2012 ACG Annual Scientific Meeting and Postgraduate
Course, Las Vegas, NV, October 22, 2012.
60
46
65
54
41
76
63
5145
35
12
29
0
20
40
60
80
100
6 months 1 Year 3 Years
Survival
(%)
Lac (n=58)
Lac/RFX (n=55)
RFX (n=28)
None (n=44)
Lac vs. Lac/RFX, P=0.057; Lac vs. RFX, P=0.049
Long Term Survival Following OHE Depends on Post-Hospital Discharge
Therapy
Neff GW et al. Abstract P927. Poster presentation at the 2012 ACG Annual Scientific Meeting and Postgraduate
Course, Las Vegas, NV, October 22, 2012.
Survival
(%)
RFX (n=28)
Lac/RFX (n=55)
Lac (n=58)
None (n=44)
Lac vs. Lac/RFX, P=0.057; Lac vs. RFX, P=0.049
65
54
63
45
35
46
29%
60
41%
51%
76
12%
0
20
40
60
80
100
0 6 12 18 24 30 36
Months
Long Term Survival Following Overt
Hepatic Encephalopathy: Conclusion
Neff GW et al. Abstract P927. Poster presentation at the 2012 ACG Annual Scientific Meeting and Postgraduate
Course, Las Vegas, NV, October 22, 2012.
• The results reveal improvement in short and
long-term survival with the addition of rifaximin
to post discharge management of patients
following hospitalization for OHE compared to
lactulose monotherapy or no therapy
Readmission Rates and Maintenance
of Overt Hepatic Encephalopathy
Neff G, Kemmer N, Cece E, Parkinson E,
Christian M, Palamittam D, Cooper J,
Mendoza A, Alsina A
Abstract P1349, Poster Presentation
ACG 2012 Annual Scientific Meeting and
Postgraduate Course
Las Vegas, NV
October 23, 2012
Readmission Rates and Maintenance of
Overt Hepatic Encephalopathy: Objective
• Objective: To evaluate the economic
differences (primarily hospitalizations)
associated with the various medical therapies
for overt hepatic encephalopathy (OHE)
Neff GW et al. Abstract P1349. Poster presentation at the 2012 ACG Annual Scientific Meeting and Postgraduate
Course, Las Vegas, NV, October 23, 2012.
Readmission Rates and Maintenance of
Overt Hepatic Encephalopathy: Methods
• Medical charts of outpatient and hospitalized patients
admitted for OHE between December 2010 and May
2012 were examined
• Information retrieved included MELD score, post-
discharge HE management protocol, HE
hospitalization number (frequency) and time to
readmission (days, range), and health insurance
coverage
• Discharge therapies analyzed:
– Group 1: Lactulose (Lac) monotherapy
– Group 2: Rifaximin (RFX) monotherapy
– Group 3: Lac/RFX combination therapy
Neff GW et al. Abstract P1349. Poster presentation at the 2012 ACG Annual Scientific Meeting and Postgraduate
Course, Las Vegas, NV, October 23, 2012.
Readmission Rates and Maintenance of
Overt Hepatic Encephalopathy: Methods
• RFX dose was 1,100 mg/day (550 mg twice daily); Lac
dose was 30 to 120 mL/day adjusted to acquire 2 to 3
loose of soft bowel movements
• Time from discharge to readmission and adherence to
follow-up visits, maintenance of family support, and
employment were measured
• Patients were divided according to compliance or
noncompliance with outpatient follow-up
Neff GW et al. Abstract P1349. Poster presentation at the 2012 ACG Annual Scientific Meeting and Postgraduate
Course, Las Vegas, NV, October 23, 2012.
Economic Differences According to Treatment:
Patients Compliant with Follow-Up
Neff GW et al. Abstract P1349. Poster presentation at the 2012 ACG Annual Scientific Meeting and Postgraduate
Course, Las Vegas, NV, October 23, 2012.
Treatment n Events MELD
Score
(mean)
Length of
Time to
Admission
Medicaid
Time to
Admission
Medicare
Time to
Admission
Insured
Time to
Admission
Lac 21 44 12.2 55 25 66
RFX 10 15 13.5 65 33 48 55
Lac + RFX 18 30 13.0 56 32 50 45
Treatment Medication
(Lac 720/yr;
RFX 13,200/yr)
HCUP
38,500/6
days
Combined
Total Cost
Total Mean
Cost Per
Patient
Cost
Range Per
Patient
P
Value
Lac 73,440 3,927,000 4,000,440 61,545 39,220 -
122, 545
RFX 422,400 847,000 1,269,400 39,669 14,609 -
90,450
0.025
Lac + RFX 570,720 1,501,500 2,072,220 50,542 26,339 -
105,666
0.055
Economic Differences According to
Treatment: Patients Non-Compliant with Follow-Up
Neff GW et al. Abstract P1349. Poster presentation at the 2012 ACG Annual Scientific Meeting and Postgraduate
Course, Las Vegas, NV, October 23, 2012.
Treatment n Events MELD
Score
(mean)
Length of
Time to
Admission
Medicaid
Time to
Admission
Medicare
Time to
Admission
Insured
Time to
Admission
Lac 21 44 12.2 55 25 66
RFX 10 15 13.5 65 33 48 55
Lac + RFX 18 30 13.0 56 32 50 45
Treatment Medication (Lac
720/yr; RFX
13,200/yr)
HCUP
38,500/6
days
Combined
Total Cost
Total Mean
Cost Per
Patient
P Value
Lac 15,120 1,694,000 1,709,120 81,387
RFX 132,000 577,500 709,500 70,950 0.035
Lac + RFX 252,680 693,000 945,680 52,538 0.065
HE Readmissions According to Treatment:
Patients Non-Compliant with Follow-Up
Neff GW et al. Abstract P1349. Poster presentation at the 2012 ACG Annual Scientific Meeting and Postgraduate
Course, Las Vegas, NV, October 23, 2012.
Treatment n Events Frequency of
2nd Admission
(%)
Time to 2nd
Admission
(Days)
Frequency of
3rd Admission
(%)
Time to 3rd
Admission
(Days)
Lac 21 44 66% 55 40% 59
RFX 10 15 40% 110 10% 145
Lac + RFX 18 30 48% 54 15% 58
Readmission Rates and Maintenance of Overt Hepatic Encephalopathy:
Conclusion
• Choice of maintenance therapy following an
OHE episode has a significant effect on overall
costs associated with overt hepatic
encephalopathy
• Rifaximin is nearly 50% more cost efficient
than lactulose monotherapy or lactulose/
rifaximin combination therapy
– Rifaximin therapy results in less frequent
hospitalizations and longer intervals between
readmissions
Neff GW et al. Abstract P1349. Poster presentation at the 2012 ACG Annual Scientific Meeting and Postgraduate
Course, Las Vegas, NV, October 23, 2012.
Randomized, Controlled, Double Blind
Study of Glycerol Phenylbutyrate in
Patients with Cirrhosis and Episodic
Hepatic Encephalopathy
Rockey DC, Vierling JM, Mantry PS, Ghabril M, Brown RS, Alexeeva O,
Zupanets IA, Grinevich VB, Baranovsky A, Dudar LV, Fadieienko G,
Kharchenko N, Klyaryts`ka I, Morozov VG, Grewal P, McCashland TM,
Reddy KG, Reddy KR, Syplyviy V, Bass NM, Dickinson K, Norris C,
Coakley DF, Mokhtarani M, Scharschmidt BF
Abstract 112, Oral Presentation The Liver Meeting 2012
The 63rd Annual Meeting of the American Association for the Study of Liver Diseases
Boston, MA November 12, 2012
Glycerol Phenylbutyrate in Patients with Cirrhosis and Episodic Hepatic
Encephalopathy: Objective
• Objective: To evaluate the efficacy and safety of
glyceryl tri(4phenylbutyrate) [GPB] in patients
with episodic hepatic encephalopathy (HE)
– GPB is an investigational drug which lowers ammonia
(NH3) through metabolism to phenylacetylglutamine, a
urea surrogate excreted in urine
Rockey DC et al. Abstract 112. Oral presentation at The Liver Meeting 2012, Boston, MA, November 12, 2012.
Glycerol Phenylbutyrate in Patients with Cirrhosis and Episodic Hepatic
Encephalopathy: Methods
• Randomized, placebo-controlled, double-blind
study
• Enrolled patients with 2 West Haven Grade 2
HE episodes in the prior 6 months while on
standard of care (SOC, lactulose and/or
rifaximin)
– Enrollment stratified for rifaximin use
• Patients could remain on study and SOC could
be changed after their first HE event
Rockey DC et al. Abstract 112. Oral presentation at The Liver Meeting 2012, Boston, MA, November 12, 2012.
Glycerol Phenylbutyrate in Patients with Cirrhosis and Episodic Hepatic
Encephalopathy: Methods (cont)
• Primary endpoint: Proportion of patients with at
least one HE event
• Secondary endpoints: Total HE events,
hospitalizations, symptomatic days as assessed
using Clinical Hepatic Encephalopathy Staging
Scale (CHESS), and venous NH3
Rockey DC et al. Abstract 112. Oral presentation at The Liver Meeting 2012, Boston, MA, November 12, 2012.
Glycerol Phenylbutyrate in Patients with Cirrhosis and Episodic Hepatic
Encephalopathy: Results
Rockey DC et al. Abstract 112. Oral presentation at The Liver Meeting 2012, Boston, MA, November 12, 2012.
All Patients GPB Placebo P value
Number of patients 90 88 --
Patients with at least one HE
event (ITT; 1° analysis)
21% 36% 0.021
Total HE events 35 57 0.035
Days with CHESS score 3 13 27 0.015
HE hospitalizations 13 25 0.064
HE hospital days 66 134 NA
NH3‒time-normalized AUC
(mol/L)
45 58 0.037
Glycerol Phenylbutyrate in Patients with Cirrhosis and Episodic Hepatic Encephalopathy: Results (cont)
Rockey DC et al. Abstract 112. Oral presentation at The Liver Meeting 2012, Boston, MA, November 12, 2012.
Rifaximin naive GPB Placebo P value
Number of patients 60 59 --
Patients with at least one HE
event
10% 32% 0.003
Patients with an HE event,
WH 2
5% 28% 0.001
Total HE events 6 19 0.0002
Glycerol Phenylbutyrate in Patients with Cirrhosis and Episodic Hepatic Encephalopathy: Results (cont)
Rockey DC et al. Abstract 112. Oral presentation at The Liver Meeting 2012, Boston, MA, November 12, 2012.
Rifaximin at baseline GPB Placebo P value
Number of patients 30 29 --
Patients with at least one HE event
13% 13% 0.909
HE hospitalizations 11 20 0.095
HE Hospital days 57 90 NA
Rifaximin at baseline or after 1st event
Number of patients 31 38 --
Patients with at least one HE event
13% 22% 0.190
Glycerol Phenylbutyrate in Patients with Cirrhosis and Episodic Hepatic Encephalopathy: Results (cont)
Rockey DC et al. Abstract 112. Oral presentation at The Liver Meeting 2012, Boston, MA, November 12, 2012.
• The study met its primary and key secondary
endpoints
• GBP significantly reduced NH3
– Reduction correlated with HE events at baseline
(P=0.0001) and during the study (P=0.0109)
Glycerol Phenylbutyrate in Patients with Cirrhosis and Episodic Hepatic Encephalopathy: Results (cont)
Rockey DC et al. Abstract 112. Oral presentation at The Liver Meeting 2012, Boston, MA, November 12, 2012.
• Adverse events (AEs) were similar on GPB (78.9%) vs.
placebo (76.1%)
– Most common: Nausea, diarrhea, abdominal pain and
increased AST
• There were no changes in MELD score, liver or other
laboratory tests
• 3 patients died (2 on GPB, 1 on placebo; all unrelated)
• Serious AEs occurred in 20 patients on GPB (1 related)
and 12 patients on placebo (4 related)
– GI bleeding and UTIs were the most common
– 66% of Child-Pugh C patients experienced SAEs
Glycerol Phenylbutyrate in Patients with Cirrhosis and Episodic Hepatic Encephalopathy: Conclusion
• GPB reduces HE events in patients with
episodic HE
• NH3 is important in HE pathogenesis
• GPB warrants further development for the
treatment of HE
Rockey DC et al. Abstract 112. Oral presentation at The Liver Meeting 2012, Boston, MA, November 12, 2012.
The Stroop Smartphone App is a Short
and Valid Screening Tool for Minimal
Hepatic Encephalopathy
Bajaj J, White M, Noble N, Monteith P, Sterling RK,
Heuman DM, Gilles HC, Stravitz R, Sanyal AJ, Fuchs M,
Puri P, Luketic VA, Wade J
Abstract 123, Oral Presentation
The Liver Meeting 2012
The 63rd Annual Meeting of the American Association
for the Study of Liver Diseases
Boston, MA
November 12, 2012
Stroop Smartphone App as Screening Tool for Minimal Hepatic
Encephalopathy: Objective
• Stroop tasks have been used to evaluate
psychomor speed and cognitive flexibility and
are now available as a smartphone app
• Objective: To validate the Stroop task iPod app
for MHE screening
Bajaj J et al. Abstract 123. Oral presentation at The Liver Meeting 2012, Boston, MA, November 12, 2012.
Stroop Smartphone App as Screening Tool for Minimal Hepatic
Encephalopathy: Methods
• Stroop app has 2 settings:
– Off: Subject identifies colors presented without words
– On: Subject identifies colors of words written in discordant
colors (e.g., “green” is written in blue color)
• Each run has 10 stimuli; a mistake ends the run
immediately
• 2 training runs given for both settings
• Actual task run until 3 correct runs achieved
• Output: Time needed to complete the correct runs and
number of trials needed to achieve 3 correct runs
Bajaj J et al. Abstract 123. Oral presentation at The Liver Meeting 2012, Boston, MA, November 12, 2012.
Stroop Smartphone App as Screening Tool for Minimal Hepatic
Encephalopathy: Methods (cont)
• Cirrhotics with/without overt hepatic
encephalopathy (OHE) and age/education-
matched healthy controls tested using the
psychometric hepatic encephalopathy battery
(PHES score <-6 = minimal hepatic
encephalopathy [MHE]) and the iPod Stroop app
• Outcomes compared:
– Cirrhosis with/without MHE and OHE
– Test/retest reliability (a subgroup was tested twice)
– External validity (before and after MHE treatment)
Bajaj J et al. Abstract 123. Oral presentation at The Liver Meeting 2012, Boston, MA, November 12, 2012.
Stroop Smartphone App as Screening Tool for Minimal Hepatic Encephalopathy: Results
*P<0.05 compared to controls; P<0.05 compared to no-MHE
Bajaj J et al. Abstract 123. Oral presentation at The Liver Meeting 2012, Boston, MA, November 12, 2012.
Controls
(n=47)
All cirrhotics (n=86)
Cirrhotics without OHE (n=58)
MHE (n=38)
no MHE (n=48)
MHE (n=23)
no MHE (n=35)
Stroop off time (sec)
35.5 5.2
57.0 13.1*
41.3 7.2
50.8 10.9*
40.6 6.8
Stroop on time (sec)
43.2 6.5
71.3 20.7*
50.2 9.3
62.5 13.6*
49.2 9.5
No. of trials for 3 correct off (median)
3 3.5* 3.5 3 3
No. of trials for 3 correct on (median)
3 4* 3 3 3
Stroop Smartphone App as Screening Tool for Minimal Hepatic
Encephalopathy: Results (cont)
Bajaj J et al. Abstract 123. Oral presentation at The Liver Meeting 2012, Boston, MA, November 12, 2012.
• Test-Retest reliability
– 15 subjects underwent Stroop Test twice 45 15
days apart
– There was no significant difference
• Off: Pre 42.5 sec; post 41.2 sec (P=0.4)
• On: Pre 50.2 sec; post 47.8 sec (P=0.08)
• External validity
– MHE treatment significantly reduced time taken on
Stroop
• Off: Pre 48 sec; post 44 sec (P=0.02)
• On: Pre 61 sec; post 55.3 sec (P=0.009)
Stroop Smartphone App as Screening Tool for Minimal Hepatic
Encephalopathy: Results (cont)
Bajaj J et al. Abstract 123. Oral presentation at The Liver Meeting 2012, Boston, MA, November 12, 2012.
• ROC/sensitivity
– Total time in Stroop off state >45.5 seconds had
highest AUC and sensitivity for MHE diagnosis
• All patients: AUC = 0.89; sensitivity = 90%
• Patients without OHE: AUC = 0.83; sensitivity = 87%
• Testing/training time was <6 minutes
Stroop Smartphone App as Screening Tool for Minimal Hepatic
Encephalopathy: Conclusion
• Stroop task, using a smart phone app, is a quick,
reliable and valid tool for diagnosing MHE
Bajaj J et al. Abstract 123. Oral presentation at The Liver Meeting 2012, Boston, MA, November 12, 2012.
Efficacy and Safety of a Probiotic
Preparation in the Secondary Prophylaxis
of Hepatic Encephalopathy in Cirrhotic
Patients: Interim Results of a Double Blind,
Randomized, Placebo Controlled Study
Dhiman RK, Rana BS, Garg A, Khattri A, Chopra M,
Thumburu KK, Malhotra S, Duseja AK, Chawla YK
Abstract 124, Oral Presentation
The Liver Meeting 2012
The 63rd Annual Meeting of the American Association
for the Study of Liver Diseases
Boston, MA
November 12, 2012
Probiotic Preparation in the Secondary Prophylaxis of Hepatic Encephalopathy:
Objective
• Objective: To assess the efficacy of a probiotic
preparation for the prevention of HE recurrence,
the reduction in hospitalizations, and in
improving the severity of liver disease in cirrhotic
patients
Dhiman RK et al. Abstract 124. Oral presentation at The Liver Meeting 2012, Boston, MA, November 12, 2012.
Probiotic Preparation in the Secondary Prophylaxis of Hepatic Encephalopathy:
Methods
• Randomized, double-blind, placebo-controlled trial
• 103 patients with liver cirrhosis who have recovered from
an episode of HE during the previous 1 month were
randomly assigned to receive for 6 months either:
– Probiotic preparation (VSL#3, CD Pharma India Pvt. Ltd,
New Delhi) at a dose of 900 billion bacteria daily (n=51)
– Placebo (n=52)
• Primary efficacy end point: Time to first breakthrough
episode of HE
• Key secondary end points: Time to hospitalization,
improvement in severity of liver disease, and blood
ammonia and cytokine levels
Dhiman RK et al. Abstract 124. Oral presentation at The Liver Meeting 2012, Boston, MA, November 12, 2012.
Probiotic Preparation in the Secondary Prophylaxis of Hepatic Encephalopathy:
Results
Dhiman RK et al. Abstract 124. Oral presentation at The Liver Meeting 2012, Boston, MA, November 12, 2012.
Probiotic
(n=51)
Placebo
(n=52)
Hazard Ratio;
(95% CI);
P value
Hospitalizations
overall (%)
19.6% 42.3% 0.45
(0.21-0.95)
0.036
Hospitalizations
involving HE (%)
15.7% 36.5% 0.42
(0.18-0.95)
0.037
• There was a trend in the reduction in the risk of an HE
episode for probiotic, as compared with placebo, over a
6-month period [Hazard ratio 0.66 (95% CI, 0.33-1.34);
P=0.258]
Probiotic Preparation in the Secondary Prophylaxis of Hepatic Encephalopathy:
Results
Dhiman RK et al. Abstract 124. Oral presentation at The Liver Meeting 2012, Boston, MA, November 12, 2012.
Probiotic (n=51)
Placebo (n=52)
Baseline After 6 months
P value
Baseline
After 6 months
P value
CTP score (95% CI)
8.5 (7.6-9.4)
7.2 (6.6-7.8)
0.009 7.9 (7.1-8.5)
6.6 (5.5-7.8)
0.08
Serum IL-6 (95% CI)
60.3 (35.8-84.7)
33.4 (19.4-47.3)
0.007 82.5 (28-137)
38 (19.9-56)
0.09
Blood ammonia
No significant
change
No significant
change
• The incidence of adverse events reported during the
study was similar in the two groups; there was no serious
adverse event
Probiotic Preparation in the Secondary Prophylaxis of Hepatic Encephalopathy:
Conclusion
• Treatment with probiotic over a 6-month period
significantly reduced:
– The risk of hospitalization involving HE
– CTP score
– IL-6 levels
Dhiman RK et al. Abstract 124. Oral presentation at The Liver Meeting 2012, Boston, MA, November 12, 2012.
A Randomized Trial of Polyethylene Glycol
3350-Electrolyte Solution (PEG) and
Lactulose for Patients Hospitalized with
Acute Hepatic Encephalopathy
Rahimi RS, Singal AG, Cuthbert JA, Rockey DC
Abstract 1546, Poster Presentation
The Liver Meeting 2012
The 63rd Annual Meeting of the American Association
for the Study of Liver Diseases
Boston, MA
November 12, 2012
PEG 3350-Electrolyte Solution and Lactulose for Acute Hepatic Encephalopathy: Objective
• Prior animal models suggest that polyethylene
glycol may be effective at clearing gut bacteria
and reducing bacterial ammoniagenesis
• Objective: To compare polyethylene glycol
3350-electrolyte solution (PEG, Golytely) and
lactulose for the treatment of acute HE in
hospitalized patients
Rahimi RS et al. Abstract 1546. Poster presentation at The Liver Meeting 2012, Boston, MA, November 12, 2012.
PEG 3350-Electrolyte Solution and Lactulose for Acute Hepatic Encephalopathy: Methods
• Study involved patients with cirrhosis of any etiology
hospitalized with HE at Parkland Memorial Hospital
– Patients with causes of altered mental status other than HE were
excluded
• Randomized patients 1:1 to receive lactulose per
standard of care or PEG
• Severity of HE measured using hepatic encephalopathy
scoring algorithm (HESA) at baseline and 24 hours
• Primary outcome: Absolute difference in HESA score at
24 hours
• Secondary outcome: Length of hospitalization
Rahimi RS et al. Abstract 1546. Poster presentation at The Liver Meeting 2012, Boston, MA, November 12, 2012.
PEG 3350-Electrolyte Solution and Lactulose for Acute Hepatic
Encephalopathy: Results
Lactulose
(n=25)
PEG
(n=23)
P value
Baseline MELD score 18 15 0.94
Baseline Child Pugh
score
9 10 0.31
Baseline ammonia level 141 152 0.95
Mean HESA score
Baseline
24 hour value
2.3
1.6
2.3
0.9
--
0.002
Median length of
hospitalization (days)
3 2 0.11
Rahimi RS et al. Abstract 1546. Poster presentation at The Liver Meeting 2012, Boston, MA, November 12, 2012.
PEG 3350-Electrolyte Solution and Lactulose for Acute Hepatic
Encephalopathy: Conclusions
• Peg improved HE over the first 24 hours of
hospitalization significantly faster than lactulose
and may result in shorter lengths of
hospitalization
• Data suggest that PEG may be superior to
lactulose for treatment of patients hospitalized
for acute HE
Rahimi RS et al. Abstract 1546. Poster presentation at The Liver Meeting 2012, Boston, MA, November 12, 2012.
A Critical Flicker Frequency Value of 32 Hz
Predicts Recurrence of Overt Hepatic
Encephalopathy in a Double-Blind, Placebo
Controlled Trial of Rifaximin in Patients
with Cirrhosis
Butterworth RF, Golden PL, Bortey E,
Paterson C, Forbes WP
Abstract 1548, Poster Presentation
The Liver Meeting 2012
The 63rd Annual Meeting of the American Association
for the Study of Liver Diseases
Boston, MA
November 12, 2012
Critical Flicker Frequency Value of 32 Hz Predicts Recurrence of Overt Hepatic
Encephalopathy in Rifaximin Trial: Ojective
• Objective: To evaluate the association between
the Critical Flicker Frequency (CFF) test and
hepatic encephalopathy (HE) as assessed by
the Conn score (CS) and to determine the time
weighted average (TWA) frequency that is
predictive of overt HE
Butterworth RF et al. Abstract 1548. Poster presentation at The Liver Meeting 2012, Boston, MA, November 12, 2012.
Critical Flicker Frequency Value of 32 Hz Predicts Recurrence of Overt Hepatic
Encephalopathy in Rifaximin Trial: Methods
• Rifaximin 550 mg BID for 6 months was evaluated in
patients with cirrhosis who had 2 episodes of HE (CS
2) or CS and asterixis grade increase of 1 each if
baseline CS=0.
• CFF (average of 8 replicate measurements) was
measured at baseline and biweekly
• Area under the curve for CFF was normalized to time on
study to calculate time-weighted average (TWA)
Butterworth RF et al. Abstract 1548. Poster presentation at The Liver Meeting 2012, Boston, MA, November 12, 2012.
Critical Flicker Frequency Value of 32 Hz Predicts Recurrence of Overt Hepatic
Encephalopathy in Rifaximin Trial: Results
• Of 299 patients randomized to rifaximin (n=140)
or placebo (n=159), 104 patients experienced
HE (31 rifaximin and 73 placebo)
• Mean TWA correlated with overt HE (Spearman
correlation coefficient= -0.62; P<0.0001)
• Area under the ROC curve value for CFF was
0.88 (95% CI= 0.84-0.92), reflecting high degree
of predictive accuracy
Butterworth RF et al. Abstract 1548. Poster presentation at The Liver Meeting 2012, Boston, MA, November 12, 2012.
Critical Flicker Frequency Value of 32 Hz Predicts Recurrence of Overt Hepatic
Encephalopathy in Rifaximin Trial: Results
• Increasing quartiles of TWA were associated
with lower rates of HE events (P<0.0001):
– CFF Q1: 11 Hz
– CFF Q2: >11 to 32 Hz
– CFF Q3: >32 to 38 Hz
– CFF Q4: >38 Hz
• An optimal TWA cut-off of 32 Hz was predictive
of overt HE (hazard ratio=0.44, 95% CI=0.020-
0.097, p<0.0001)
Butterworth RF et al. Abstract 1548. Poster presentation at The Liver Meeting 2012, Boston, MA, November 12, 2012.
Critical Flicker Frequency Value of 32 Hz Predicts Recurrence of Overt Hepatic
Encephalopathy in Rifaximin Trial: Conclusion
• The CFF test independently predicted
brreakthrough HE
• A cut-off of 32 Hz was predictive of overt HE
• Findings establish CFF as a viable alternative or
adjunct to CS grading of HE in patients with
cirrhosis
Butterworth RF et al. Abstract 1548. Poster presentation at The Liver Meeting 2012, Boston, MA, November 12, 2012.
Oral Branched-Chain Amino Acids for
Hepatic Encephalopathy: Systematic
Review of Individual Patient Data from
Randomized Clinical Trials
Gluud LL, Dam G, Borre M, Les I, Cordoba J, Marchesini G,
Aagaard NK, Risum N, Vilstrup HV
Abstract 1584, Poster Presentation
The Liver Meeting 2012
The 63rd Annual Meeting of the American Association
for the Study of Liver Diseases
Boston, MA
November 12, 2012
Oral Branched Chain Amino Acids for Hepatic Encephalopathy Review:
Objective
• Objective: To systematically review effects of
oral branched chain amino acids (BCAAs) vs.
control supplements or placebo for patients with
recurrent overt or minimal hepatic
encephalopathy (HE)
Gluud LL et al. Abstract 1584. Poster presentation at The Liver Meeting 2012, Boston, MA, November 12, 2012.
Oral Branched Chain Amino Acids for Hepatic Encephalopathy Review:
Methods
• Analyzed data from 8 randomized trials
identified via electronic and manual searches
• Analyses included data on 382 patients with
cirrhosis and HE
• Data retrieved by corresponding with the authors
of the trials or from published reports
– Individual patient data were available for 4 trials with
255 patients
– Trial-level data were available for remaining 4 trials
Gluud LL et al. Abstract 1584. Poster presentation at The Liver Meeting 2012, Boston, MA, November 12, 2012.
Oral Branched Chain Amino Acids for Hepatic Encephalopathy Review: Results
• Improvements in HE manifestations were registered for 87 of 172 patients in the BCAA group vs. 56 of 210 controls
• Effect of BCAA was different for patients with overt vs. minimal HE (P=0.05 for subgroup differences):
Gluud LL et al. Abstract 1584. Poster presentation at The Liver Meeting 2012, Boston, MA, November 12, 2012.
Risk Difference, BCAA vs. Controls
(95% CI)
All patients 0.21 (0.09 - 0.34)
Overt HE 0.30 (0.16 - 0.44)
Minimal HE 0.10 (-0.05 - 0.25)
• No other predictors of intertrial heterogeneity were identified
Oral Branched Chain Amino Acids for Hepatic Encephalopathy Review: Results
(cont)
• BCAA supplements:
– Had no effect on mortality or markers of nutritional
status
– Did not induce adverse events
Gluud LL et al. Abstract 1584. Poster presentation at The Liver Meeting 2012, Boston, MA, November 12, 2012.
Oral Branched Chain Amino Acids for Hepatic Encephalopathy Review:
Conclusion
Gluud LL et al. Abstract 1584. Poster presentation at The Liver Meeting 2012, Boston, MA, November 12, 2012.
• Oral BCAA supplements improve the
manifestations of recurrent HE but have no
effect on survival
Predictors of Early Hepatic
Encephalopathy in Patients Undergoing
Transjugular Intrahepatic Portosystemic
Shunt (TIPS)
Jow AZ, Chaudhary N, Merola J, Barboza K,
Charles H, Sigal S
Abstract 1585, Poster Presentation
The Liver Meeting 2012
The 63rd Annual Meeting of the American Association
for the Study of Liver Diseases
Boston, MA
November 12, 2012
Predictors of Early Hepatic Encephalopathy Following TIPS:
Objective
• Objective: To determine predictors of overt
hepatic encephalopathy (HE) within 1 week,
specifically the effect of hyponatremia (HN), in
patients undergoing transjugular intrahepatic
portosystemic shunt (TIPS) insertion
Jow AZ et al. Abstract 1585. Poster presentation at The Liver Meeting 2012, Boston, MA, November 12, 2012.
Predictors of Early Hepatic Encephalopathy Following TIPS:
Methods
• A single-center, retrospective chart review of 114 consecutive
adult patients with cirrhosis who underwent non-emergent
TIPS insertion between 2005 and 2011 for non-variceal
bleeding indications
• Baseline clinical and laboratory patient characteristics were
collected
• A composite mean of serum Na levels was derived from the
three days prior to TIPS (pre-TIPS Na)
• Wald χ2 analysis was conducted to identify significant clinical
parameters associated with overt HE within 1 week
• Odds ratios were calculated to determine the relative risk of
developing HE for each of the predictive variables
Jow AZ et al. Abstract 1585. Poster presentation at The Liver Meeting 2012, Boston, MA, November 12, 2012.
Predictors of Early Hepatic Encephalopathy Following TIPS: Results
• 74 patients who underwent 81 TIPS procedures were
included
• Factors predictive of overt HE within 1 week:
Jow AZ et al. Abstract 1585. Poster presentation at The Liver Meeting 2012, Boston, MA, November 12, 2012.
Wald χ2 P value
Pre-tips Na 4.8 <0.05
Total bilirubin 5.6 <0.05
MELD-Na 6.1 <0.05
• A history of HE and serum creatinine levels were not
significantly associated with the development of OHE
within 1 week following TIPS insertion
Predictors of Early Hepatic Encephalopathy Following TIPS: Results
• Odds ratio for developing HE:
Jow AZ et al. Abstract 1585. Poster presentation at The Liver Meeting 2012, Boston, MA, November 12, 2012.
Clinical Parameter Odds ratio (95% CI)
Pre-tips Na <135 mEq/L 10.3 (1.3 - 83.1)
Total bilirubin >4.0 mg/dL 3.0 (0.9 - 10.0)
MELD-Na >25 5.4 (1.6 - 18.7)
• Pre-TIPS Na categories vs. incidence of overt HE within 1 week:
Na Categories Incidence of HE (%)
124 mEq/L 37.5%
125 - 130 mEq/L 24%
131 - 134 mEq/L 26%
135 mEq/L 3.4%
Predictors of Early Hepatic Encephalopathy Following TIPS:
Conclusion
• In patients with cirrhosis and portal hypertension
undergoing TIPS insertion, lower pre-TIPS Na,
higher total bilirubin, and higher MELD-Na
values were predictive of the development of
overt HE post-TIPS within 1 week
• Predictive capability of pre-TIPS Na and MELD-
Na for the development of HE indicates that
TIPS insertion in patients with low Na levels
should be undertaken with caution
Jow AZ et al. Abstract 1585. Poster presentation at The Liver Meeting 2012, Boston, MA, November 12, 2012.
Improvement of Liver Function and
Prevention of Encephalopathy by
Occlusion of Porto-Systemic Shunt in
Patients with Child-Turcott-Pugh Class B
Cirrhosis and Recurrent Hepatic
Encephalopathy
An J, Lim Y-S, Kim GA, Lee D, Shim JH, Kim KM, Lee HC,
Chung Y-H, Lee YS
Abstract 1586, Poster Presentation
The Liver Meeting 2012
The 63rd Annual Meeting of the American Association
for the Study of Liver Diseases
Boston, MA
November 12, 2012
Improvement of Liver Function and Prevention of HE by Occlusion of Porto-
Systemic Shunt: Objective
• Objective: To analyze the effect of occlusion of
large spontaneous porto-systemic shunts in
preventing the recurrence of hepatic
encephalopathy (HE)
An J et al. Abstract 1586. Poster presentation at The Liver Meeting 2012, Boston, MA, November 12, 2012.
Improvement of Liver Function and Prevention of HE by Occlusion of Porto-
Systemic Shunt: Methods
• Data of 20 patients who underwent occlusion of
a portosystemic shunt for recurrent HE between
2006 and 2011 in a single tertiary referral
hospital were analyzed
An J et al. Abstract 1586. Poster presentation at The Liver Meeting 2012, Boston, MA, November 12, 2012.
Improvement of Liver Function and Prevention of HE by Occlusion of Porto-
Systemic Shunt: Results
• Patient demographics
– Median age: 63 years (range, 48-79 years)
– Males: 55%
– Child-Turcott-Pugh (CTP) class:
• Class B: 12
• Class C: 8
An J et al. Abstract 1586. Poster presentation at The Liver Meeting 2012, Boston, MA, November 12, 2012.
Improvement of Liver Function and Prevention of HE by Occlusion of Porto-
Systemic Shunt: Results (cont)
An J et al. Abstract 1586. Poster presentation at The Liver Meeting 2012, Boston, MA, November 12, 2012.
(n=12)
(n=8)
*
Cumulative overall survival rate after occlusion
89%
20%
Improvement of Liver Function and Prevention of HE by Occlusion of
Porto-Systemic Shunt: Results (cont)
Number
Before Occlusion
After Occlusion
Number of HE episodes and hospitalizations due to HE*
HE episodes Hospitalizations
due to HE
*3 month period before and 3 month period after occlusion
An J et al. Abstract 1586. Poster presentation at The Liver Meeting 2012, Boston, MA, November 12, 2012.
Improvement of Liver Function and Prevention of HE by Occlusion of
Porto-Systemic Shunt: Results (cont)
An J et al. Abstract 1586. Poster presentation at The Liver Meeting 2012, Boston, MA, November 12, 2012.
• Shunt occlusion failed technically in 3 patients
• The median survival time for patients with CTP class C was 4 months
• Among patients with CTP class B, comparing 3 months before and after occlusion – HE episodes decreased: 4.83 vs. 0.08, P<0.01
– HE hospitalizations decreased: 1.67 vs. 0.08, P<0.01
– CTP score improved in 9/12 (75%)
– MELD score improved in 6/12 (50%)
• Hepatic decompensation and hepatorenal syndrome after occlusion occurred in 3 CTP class 3 patients
Improvement of Liver Function and Prevention of HE by Occlusion of
Porto-Systemic Shunt: Conclusions
An J et al. Abstract 1586. Poster presentation at The Liver Meeting 2012, Boston, MA, November 12, 2012.
• Occlusion of spontaneous porto-systemic shunts
is effective in preventing HE, especially in
patients with CTP class B; improvement in liver
function can also be expected in some class B
patients
• Shunt occlusion should be cautiously considered
in patients with CTP class C
Assessing Treatment Patterns in Patients
With Overt Hepatic Encephalopathy
Neff GW, Frederick RT
Abstract 1612, Poster Presentation
The Liver Meeting 2012
The 63rd Annual Meeting of the American Association
for the Study of Liver Diseases
Boston, MA
November 12, 2012
Treatment Patterns in Cirrhotic Patients Following an Overt HE Episode:
Objective • Background:
– Overt hepatic encephalopathy (OHE) is associated with a
substantial medical and financial burden
– Patients who have had OHE are at increased risk of
recurrence and may experience persistent cognitive
impairment
– Treatment after an OHE episode can increase the duration
of HE remission, decrease HE-related hospitalizations,
and improve quality of life
• Objective: To examine the outpatient treatment
rates for patients who had 1 episode of OHE from
2009 to 2011
Neff GW et al. Abstract 1512. Poster presentation at The Liver Meeting 2012, Boston, MA, November 12, 2012.
Treatment Patterns in Cirrhotic Patients Following an Overt HE Episode: Methods
• Review of a subset of national claims for medical
and hospital activity from January 2009 to
December 2011 collected by Source Healthcare
Analytics
– Patient selection based on claims with and ICD-9
code 572.2 (HE) and any filled prescription in each
calendar year
– Claims from eligible patients were examined for any
filled prescription for rifaximin (RFX), lactulose (Lac)
or RFX + Lac as an indicator of ongoing treatment
Neff GW et al. Abstract 1512. Poster presentation at The Liver Meeting 2012, Boston, MA, November 12, 2012.
Treatment Patterns in Cirrhotic Patients Following an Overt HE Episode: Results
Neff GW et al. Abstract 1512. Poster presentation at The Liver Meeting 2012, Boston, MA, November 12, 2012.
Year Eligible
Patients with
OHE
% of Eligible
Patients with
Inpatient
Claims
% of Eligible
Patients
Receiving
Ongoing
Treatment
2009 13,623 89.2% 39.7%
2010 15,529 87.8% 37.7%
2011 16,328 86.4% 36.1%
Treatment Patterns in Cirrhotic Patients Following an Overt HE Episode: Results
Neff GW et al. Abstract 1512. Poster presentation at The Liver Meeting 2012, Boston, MA, November 12, 2012.
27.9%
8.1%
3.9%
14.1%
8.8%
13.2%
0
5
10
15
20
25
30
RFX Alone RFX + Lac Lac Alone
% of
OHE
Patients
Change in treatment paradigm, 2009 vs. 2011
2009
2011
Treatment Patterns in Cirrhotic Patients Following an Overt HE Episode:
Conclusions
Neff GW et al. Abstract 1512. Poster presentation at The Liver Meeting 2012, Boston, MA, November 12, 2012.
• Despite medical and financial advantages of treatment
after an episode of OHE, results suggest that majority of
patients remain untreated as outpatients (63.9% in 2011)
• Treatment paradigm appears to have shifted following
approval of RFX in 2010
• Whether low treatment rates are result of patients failing
to fill prescriptions (lack of insurance, other financial
concerns, and/or noncompliance) remains unclear
• Understanding causes of and correcting the apparent
undertreatment of HE is essential